Immune-related adverse events (irAEs) and outcome in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts) treated by immune-checkpoints inhibitors (ICI)
| Autor: | N. Baste Rotllan, F.R. Ferrand, Stéphane Champiat, François Bidault, Odile Casiraghi, M. Iacob, Aurélien Marabelle, D. Bouguetta, A. Sampetrean, Stéphane Temam, L. Mayache Badis, Pierre Blanchard, Caroline Even, P. Gorphe, Anne Auperin |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Potential impact medicine.medical_specialty Standard of care business.industry Platinum compounds Retrospective cohort study Hematology medicine.disease Head and neck squamous-cell carcinoma Primary tumor stomatognathic diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine Cohort otorhinolaryngologic diseases Medicine business Adverse effect |
| Zdroj: | Annals of Oncology. 30:v470 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdz252.052 |
| Popis: | Background ICI is a standard of care in R/M HNSCC pts progressing to platinum compounds. However, few pts respond to ICI and irAEs could limit their use.There are contradictory reports regarding the association of irAEs and outcomes to ICI. The aim of this study is to further evaluate the potential impact of irAEs on outcomes for HNSCC. Methods We performed a retrospective observational study based on all R/M HNSCC pts treated by ICI in our center during 2014-19. To limit the bias due to the association between ICI administration duration, obtention of objective response (OR) and occurrence of irAE, a Landmark analysis method with 90 days (d) cut-off was used. Results We included 103 R/M HNSCC pts (80% male, 73% smokers). Primary tumor locations were: oropharynx (42%), oral cavity (23%), hypopharynx (18%) and larynx (17%). ICI were administered as monotherapy (43%) or combination (57%; CTLA-4 inhibitor, ICOS agonist). There were 14 responders (R) with median time to obtain OR of 102 d (8 after 90 d). Median ICI duration was 376 d in R pts and 84 d in others. irAEs were observed in 38 pts (37%), with low frequency of grade (G) 3-4 (6%). Occurrence of irAEs within the first 90 d (named early AEs) was observed in 25 pts (24%). 51 pts (50%) remained on ICI beyond 90 d, including all the 14 R: 30 pts (59%) had irAEs and 17 (33%) had early irAEs. In total cohort, OR was more frequent in pts with any irAE (32%) than in others (3%). Results were similar with irAE G2-4: 42% OR vs 5% OR. But, using landmark method, in pts who received ≥ 90 d ICI, this association was no longer observed: 35% of pts with early irAEs had OR vs 24% in other pts (p = 0.37), and 36% vs 25% for early irAEs of G2-4 (p = 0.47). Median [95%CI] PFS and OS were 3.6 months (m) [2.9-4.5] and 10.6m [7.6-13.2] in total cohort; 5.8 m [4.8-7.7] and 19.1 m [12.6-32.5] in ICI ≥90 d. Early irAEs were not associated with PFS or OS in this latter subgroup. Conclusions The impact of irAEs on outcomes could be mistaken if not taking into consideration the ICI duration because the likelihood of irAEs and OR increases with treatment duration. Using a Landmark analysis with 90 d cut-off, we did not observe an association between irAEs and outcome in R/M HNSCC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure N. Baste Rotllan: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Nanobiotix; Honoraria (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (institution): PharmaMar. All other authors have declared no conflicts of interest. |
| Databáze: | OpenAIRE |
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